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Female sex hormones and cognition in middle-aged and elderly Danish twins


Women have higher lifetime risk of developing AD than men. Additionally, women with AD tend to have lower cognitive function compared to men with AD. These sex differences raise the question of female sex hormones’ influence on cognition and risk of dementia.

During menopause, which typically occur during the fifth decade, the level of estrogen and progesterone decreases causing a wide set of menopausal symptoms, e.g. hot flashes, urinary incontinence and vaginal dryness.


Another suggested change during and post menopause is memory impairment. A part of the explanation for the latter change could be the location of the estrogen receptors, which are found not only in the ovaries and uterus, but also the brain, more specifically the hypothalamus, cortex and hippocampus with the latter two areas being associated with cognitive functions.


Systemic hormone replacement therapy (HRT) has been widely used in Denmark in the late 1980s and early 1990s to manage menopausal symptoms. Sales of HRT for menopausal symptoms in Denmark was the highest in the Nordic countries from 1980 to 1989.

During this period of time, HRT was increasingly viewed as having beneficial effects on chronic diseases related to aging, including coronary heart disease (CHD) and cognitive impairment. Nevertheless, in 2002 Women’s Health Initiative (WHI) published a randomized controlled trial, which contradicted these views regarding CHD, while the influence of HRT on cognitive function was less clear.


The WHI findings led to a change in international guidelines regarding systemic HRT, recommending that HRT be used in the smallest dose in the smallest amount of time, as the damaging effects are believed to exceed the beneficial effects. Currently, the Danish national guidelines from Danish Society of Obstetrics and Gynecology (DSOG), based on the English NICE guidelines, recommend that Danish doctors explain to menopausal females, that it is still unknown whether HRT has an effect on cognitive impairment and dementia.



To study the association between female sex hormones and cognition in mid- and late life in Danish twins.

In particular aiming at quantifying the following:

  • Lifetime-risk of accelerated cognitive decline and/or dementia in elderly Danish female twins, including comparison with males and with singletons
  • Risk of accelerated cognitive decline and/or developing dementia in elderly Danish female twins when divided according to level of endogenous female hormone exposure in Danish Twins
  • Risk of accelerated cognitive decline and/or developing dementia in female twin pairs, who had received HRT during menopause


The project is based on the Danish Twin Cohorts: Middle-aged Danish Twins (MADT) and the Longitudinal Study of Aging Danish Twins (LSADT). Furthermore those registers will be linked to the National Discharge Register and the Danish National Prescription Registry. Data has been collected from 1994 to 2010.

Included in the study are female twins born before 1950 and alive in 1995 (N=16,700), plus a random 5% sample from the Danish, female population also born before 1950 and alive in 1995 (N=59,398).



  • DARC II, Velux Grant nr. 32105.

Main supervisor


  • Professor Jesper Hallas, University of Southern Denmark
  • Professor Merete Osler, Copenhagen University
PhD Student

Laura Ekstroem Loekkegaard


EBB - Epidemiology, Biostatistics and Biodemography Department of Public Health University of Southern Denmark

  • Campusvej 55
  • Odense M - DK-5230
  • Phone: +45 6550 3029

Last Updated 20.10.2023